Faculty Bibliography

Educational initiatives that address the gap between basic/preclinical and clinical practices are important to effectively translate basic science discoveries to benefit patients. The ILAE Neurobiology Commission conducted a pilot project aimed at exposing basic and preclinical scientists engaged in epilepsy research to general clinical issues pertaining to the diagnosis and care of people with epilepsy. This aim was addressed through a two-week-long, on-site clinical training program for 50 basic scientists in 21 epilepsy centers across 18 countries in the six ILAE regions (with a maximum of 3 basic scientists per center). The learning objectives and the training module were discussed and defined by the project organizing committee, which consisted of Neurobiology Commission members and a team of epileptologists representing different geographical regions. The training activities were conducted at each epilepsy center under the local supervision of clinical tutors. Each basic scientist was exposed to 50.3 ± 23.3 (range 16-89) hours of intensive and dedicated clinical training, coordinated by 2-3 tutors per center, assisted by 6.8 ± 3.6 colleagues. A structured test consisting of 17 general clinical epilepsy questions was completed by the trainees before and after the training activity. The learning assessment was based on the comparison between responses to the exit and entry tests. After the on-site clinical exposure, the proportion of correct answers increased to 87% compared to 61% in the entry test. Structured post-training questionnaires demonstrated very high satisfaction of trainees and all involved tutors across the different aspects of the training module. This global pilot study demonstrated that on-site attendance by basic scientists in specialized clinical settings up-scaled their knowledge of clinical epileptology and facilitated networking with clinicians. Expansion of this pilot to further centers should be considered to understand how exposure to clinical practice affects research direction and quality of translational epilepsy research. PLAIN LANGUAGE SUMMARY: Epilepsy research has long benefitted from collaboration between scientists and clinicians. Early exposure of researchers to people with epilepsy and their care teams may strengthen future impact. This pilot study tested a two-week immersive experience where small teams of basic scientists shadowed clinicians during their work at hospitals around the world. Questionnaires showed high satisfaction among both groups. Results support expanding such training, with the backing of the International League Against epilepsy and aligned centers, to build understanding, interest, and long-term commitment, ensuring bench research is informed by and translates to clinical practice and improved quality of life for patients.

BACKGROUND AND OBJECTIVES/OBJECTIVE:Congenital obstructive hydrocephalus (HCP) causes progressive, irreversible fetal brain damage through ventricular enlargement and increasing fetal cerebral tissue compression. Postnatal treatments of choice include ventriculoperitoneal shunting or endoscopic third ventriculostomy (ETV). Intrauterine treatments, such as ventriculoamniotic shunting, were attempted unsuccessfully 4 decades ago and failed to improve postnatal outcomes, likely due to inadequate fetal patient selection. The aim of this study was to evaluate the efficacy of prenatal ETV for early ventricular decompression and potential prevention of fetal brain damage in hydrocephalic fetal lambs. METHODS:HCP was induced in 24 fetal lambs by injecting BioGlue into the cisterna magna at E85. Three weeks later (E105-110), fetal ETV was successfully performed on 8 fetuses using a small rigid cystoscope. Fetal brain lateral ventricular diameters and cerebral mantle thicknesses were monitored by prenatal and postnatal ultrasounds and fetal MRI. RESULTS:According to the Cincinnati HCP Severity Scale, moderate and severe HCP subgroups responded positively to fetal ETV with reduced cerebral ventricular diameters. Ten days post-ETV, severe HCP fetal lambs improved to moderate levels, whereas those with moderate HCP normalized by birth. A similar improvement pattern was seen for the mechanical compression threshold (ventricular diameters/biparietal diameter). Biparietal diameter values did not significantly differ among nontreated, treated, and normal control groups during pregnancy. MRI revealed a significant increase in brain mantle thickness in the prenatally treated fetuses. CONCLUSION/CONCLUSIONS:Prenatal ETV is feasible in hydrocephalic fetal lambs and effectively reverses ventriculomegaly and brain compression in cases of severe or moderate fetal HCP in this ovine model.

PURPOSE OF REVIEW/OBJECTIVE:Children with recurrent syncope with prolonged pauses who have failed traditional therapies may be candidates for a cardioneuroablation as an alternative to pacemaker implantation. This article reviews cardioneuroablation in the pediatric population. RECENT FINDINGS/RESULTS:Cardioneuroablation has been used in adults for cardioinhibitory syncope for more than 2 decades with promising results. Despite the heterogenous patient population and variation in technical approaches to the procedure, between 85 and 90% of patients have a significant reduction in syncope and improvement in quality of life. While the data in children is limited, reports have shown similar success. Catheter ablation of ganglionated plexuses can be performed by ablating in the right or left atrium or both. The long-term effects in disrupting the sympathovagal imbalance remains unknown. SUMMARY/CONCLUSIONS:Cardioneuroablation may be an option for select children with cardioinhibitory syncope who have failed standard medical approaches. Early results of vagal ablation in children have been promising. Future long-term registries following cardioneuroablation is needed.

BACKGROUND:Patients with Cushing's syndrome (CS) have a high prevalence of cardiovascular disease, and other recognized risk factors for atrial fibrillation/flutter (AF/AFL); however, the prevalence of AF/AFL has not been well characterized in this population. METHODS:We conducted a retrospective matched-cohort study using the Clalit Health Services database, including patients with CS and 1:5 matched controls. We assessed the risk of new-onset AF/AFL overall and according to disease etiology and remission status. Pre-existing AF/AFL was defined as >30 days before CS, and new-onset as within 30 days or thereafter. RESULTS:The cohort included 609 patients with CS and 3018 controls. Pre-existing AF/AFL was more common among patients with CS than controls (3.6% vs. 2.1%; OR 1.70, 95% CI 1.04-2.78). During a mean follow-up of 15 years, patients with CS had a significantly higher risk of developing new-onset AF/AFL compared with controls (HR 1.55, 95% CI 1.19-2.03). This increased risk was observed in both Cushing's disease (CD) (HR 1.53, 95% CI 1.01-2.32) and adrenal CS (HR 1.70, 95% CI 1.06-2.74). AF/AFL risk did not significantly differ according to remission status, although a trend toward lower risk was observed. Multivariate analysis identified older age at diagnosis, male sex, hypertension, vascular disease, and higher BMI as predictors for new-onset AF/AFL. CONCLUSION/CONCLUSIONS:CS is associated with an increased risk of AF/AFL. This elevated risk is observed across both CD and adrenal CS and persists despite disease remission, underscoring the need for heightened awareness and close cardiovascular surveillance in this population. The increased risk of AF/AFL appears to be primarily driven by coexisting cardiovascular comorbidities rather than cortisol excess or other CS-specific features.

OBJECTIVE:To compare postnatal MRI outcomes after prenatal myelomeningocele repair using three different dural substitutes. METHOD/METHODS:32 sheep fetuses were included, with 34.3%(11/32) serving as healthy controls and the remaining undergoing prenatal spinal lumbar defect creation to recreate a myelomeningocele in the fetus. 90.5% (19/21) of sheep fetuses with surgically created MMC underwent repair using traditional collagen (Durapair) patch (n = 6), HUC matrix (NEOX RT) patch (n = 6), or a novel PLA/PCL patch (n = 7). All sheep underwent brain and spine MRI within 24 h after delivery. Images were reviewed in Research PACS by a pediatric neuroradiologist and were assessed for ventricle size, degree of hindbrain herniation, spinal cord integrity, and fluid collection at the repair site. RESULTS:There was a significant reduction in hindbrain herniation in all three intervention groups when compared with MMC without prenatal intervention. There was increased incidence of complete spinal cord defect (3/7), pseudomeningocele (5/7) and intraspinal cyst (2/7) at the repair site of the PLA/PCL patch compared with the Durapair and NEOX RT patches. CONCLUSIONS:This study demonstrates equal efficacy in reducing hindbrain herniation in MMC repair by Durapair, NEOX RT, and PLA/PCL patches by MRI. Future studies analyzing the interaction of the patches with the host tissue in animal models and clinical trials will help to better determine the true safety and efficacy of these novel patches for clinical use.

AIMS/UNASSIGNED:Femoral nerve palsy is a potential complication of brace treatment for children with developmental dysplasia of the hip (DDH). Little is known about its causes, and previous studies have been limited by their small sample size, retrospective design, and/or being single-centre series. The aim of this study was to examine the risk factors for femoral nerve palsy in the largest prospective cohort of children to date with DDH treated using an orthosis. METHODS/UNASSIGNED:A global multicentre prospective database of children with DDH was analyzed. Those treated primarily using an orthosis were included. Mixed-effects logistic regression was used to identify risk factors for the development of femoral nerve palsy, including sex, age at the time of diagnosis and application of an orthosis, the type of orthosis, the location of the femoral head, femoral head cover, and α angle. Both univariate and multivariate analyses were conducted. RESULTS/UNASSIGNED:The study included 3,008 children (5,012 affected hips) who were enrolled from 21 centres in seven countries; 99 hips (2.0%) in 94 children (3.1%) developed a femoral nerve palsy, which occurred at a median of seven days (IQR 6 to 21) after the application of a brace. A significantly increased proportion of children who developed a femoral nerve palsy were treated in a Pavlik harness compared with those who did not develop a femoral nerve palsy (84.0% (n = 79) vs 61.9% (n = 1,804); p < 0.001). Univariate analyses identified a lower percent cover of the femoral head (odds ratio (OR) 0.87 (95% CI 0.84 to 0.91); p < 0.001) and lower α angle (OR 0.82 (95% CI 0.76 to 0.89); p < 0.001) to be significantly associated with the development of femoral nerve palsy. These risk factors remained significant in the multivariate model. CONCLUSION/UNASSIGNED:This is the largest multinational study to date evaluating the incidence and risk factors for the development of a femoral nerve palsy in these children. The incidence of femoral nerve palsy was 3.1%. The severity of DDH was identified as a significant risk factor for its development. The use of a Pavlik harness was significantly associated with the development of a femoral nerve palsy. Understanding the factors which influence its development will be important to optimize outcomes of treatment in children with DDH.

UNLABELLED:<p>Introduction: Tremor-predominant Parkinson's disease (TPPD) generally responds favorably to deep brain stimulation (DBS) targeting the subthalamic nucleus (STN). However, traditional stereotactic targeting of the STN does not universally yield the anticipated intraoperative improvement, prompting exploration of additional targets to achieve optimal results prior to permanent implantation of electrodes. The posterior subthalamic area (PSA), including the caudal zona incerta (cZI), have been associated with tremor suppression and can be easily compared to the neighboring STN intraoperatively. METHODS:We retrospectively compared intraoperative and clinical outcomes in tremor-dominant PD patients who prospectively underwent dual trajectory microelectrode monitor targeting the STN and PSA/cZI. We compared the neurophysiology and tremor response of both the central (STN) and posterior (PSA) trajectories in 22 patients and analyzed outcomes in those who ultimately received traditional STN (16) or PSA/cZI lead implantation (12). RESULTS:While both groups achieved substantial overall motor improvement under chronic stimulation, intraoperative test stimulation through the posterior path produced more consistent tremor arrest compared with STN. These findings suggest that positioning the DBS lead further posteriorly to engage the PSA can augment tremor suppression in select cases of TPPD without compromising other parkinsonian symptom relief. CONCLUSION/CONCLUSIONS:Our results emphasize the value of intraoperative physiological feedback in trajectory selection in tremor-predominant patients and are consistent with emerging literature that PSA/cZI DBS is an effective and potentially superior target for management of tremor in PD. </p>.

OBJECTIVES/OBJECTIVE:Congenital high airway obstruction syndrome (CHAOS) is characterized by over-distended lungs leading to impaired cardiac return and fetal hydrops. Survivors have been reported following prenatal spontaneous fistulization, fetal procedures to decompress the airway, or ex-utero intrapartum treatment (EXIT). The long-term outcomes of survivors are unclear. METHODS:We performed a retrospective chart review on patients diagnosed with CHAOS in our center between 2005-2025. RESULTS:Of the 28 patients with CHAOS, three (10.7%) underwent a fetal procedure to decompress the airway. Three patients (10.7%) had evidence of spontaneous fistulization. Four patients (14.3%) terminated the pregnancy and four (14.3%) had in-utero fetal demise. Twenty patients (71.4%) were live-born; of these, 14 (70%) died shortly after delivery and two (10%) died in the neonatal period. Seven patients (35%) underwent EXIT-to-tracheostomy at our center, of which four (57.1%) are long-term survivors ranging in age from 4 to 19 years old. Three patients have undergone airway reconstruction between 1.6 and 5.6 years of age; one remains tracheostomy-dependent due to recurrent airway stenosis, one patient has undergone reconstruction and is likely to be decannulated soon, and one patient had successful reconstruction and was decannulated. The fourth patient has not yet undergone airway reconstruction. CONCLUSIONS:CHAOS remains a highly morbid diagnosis, but long-term survivorship and liberation from tracheostomy is possible.